WO2024106588A1 - Peptide ayant une activité d'amélioration de l'état de la peau et son utilisation - Google Patents

Peptide ayant une activité d'amélioration de l'état de la peau et son utilisation Download PDF

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Publication number
WO2024106588A1
WO2024106588A1 PCT/KR2022/018719 KR2022018719W WO2024106588A1 WO 2024106588 A1 WO2024106588 A1 WO 2024106588A1 KR 2022018719 W KR2022018719 W KR 2022018719W WO 2024106588 A1 WO2024106588 A1 WO 2024106588A1
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Prior art keywords
peptide
skin
group
cosmetic composition
amino acid
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PCT/KR2022/018719
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English (en)
Korean (ko)
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정용지
김은미
이응지
김민웅
강한아
황보별
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(주)케어젠
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the present application relates to peptides with skin condition improving activity and their uses.
  • collagen a major component of the extracellular matrix
  • Collagen forms most of the organic matter of skin, tendons, bones, and teeth, and its content is particularly high in bones and skin (dermis). This collagen is reduced by age and photoaging caused by ultraviolet irradiation, and this is known to be closely related to the formation of wrinkles in the skin.
  • collagen plays an important role in wound healing, and by promoting collagen synthesis in damaged epithelium, wounds can be recovered quickly and without scars.
  • One aspect is to provide a peptide consisting of the amino acid sequence of SEQ ID NO: 1.
  • Another aspect is to provide a composition for improving skin condition containing a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
  • One aspect provides a peptide consisting of the amino acid sequence of SEQ ID NO: 1.
  • peptide may refer to a linear molecule formed by combining amino acid residues with each other through peptide bonds.
  • the peptide can be prepared according to chemical synthesis methods known in the art, especially solid-phase synthesis technology or liquid-phase synthesis technology (US Patent No. 5,516,891).
  • solid-phase synthesis technology or liquid-phase synthesis technology (US Patent No. 5,516,891).
  • US Patent No. 5,516,891 As a result of diligent efforts to develop a peptide with biologically effective activity, the present inventors identified a peptide consisting of the amino acid sequence of SEQ ID NO: 1.
  • the biologically effective activity includes (a) promoting proliferation of fibroblasts; (b) Enhanced expression of extracellular matrix constituents, collagen type 1 (Col1a1), fibronectin, or elastin; and (c) it may exhibit one or more characteristics selected from the following characteristics, such as enhancing the expression of skin barrier factor sirtuin-1 (SIRT-1) or aquaporin-3 (AQP3). Therefore, the peptide can be used to improve skin condition.
  • SIRT-1 skin barrier factor sirtuin-1
  • AQP3 aquaporin-3
  • the peptides may be added to N- or C- groups of the peptides to obtain chemical stability, enhanced pharmacological properties (half-life, absorption, potency, potency, etc.), altered specificity (e.g., broad spectrum of biological activity), and reduced antigenicity.
  • a protecting group may be attached to the terminal.
  • the N-terminus of the peptide is an acetyl group, a fluoreonylmethoxycarbonyl group, a formyl group, a palmitoyl group, and a myristyl group. group), a stearyl group, a butoxycarbonyl group, an allyloxycarbonyl group, and polyethylene glycol (PEG).
  • the C-terminus of the peptide may be bonded to any one protecting group selected from the group consisting of an amino group (-NH 2 ), a tertiary alkyl group, and azide (-NHNH 2 ). You can. Additionally, the peptide may optionally additionally include a targeting sequence, a tag, a labeled residue, and an amino acid sequence prepared for the specific purpose of increasing half-life or peptide stability.
  • the peptide is artificially synthesized or non-naturally occurring or engineered, and the term “non-naturally occurring or engineered” refers to not being in its natural state. , refers to a state created by applying artificial transformation.
  • the artificial modification includes artificially synthesizing an amino acid sequence by mimicking a plurality of amino acid structures or engineering it to obtain chemical stability, enhanced pharmacological properties, altered specificity, or reduced antigenicity as described above. can do.
  • the term “stability” may mean not only in vivo stability, which protects the peptide from attack by protein cleavage enzymes in vivo, but also storage stability (e.g., room temperature storage stability).
  • Another aspect provides a cosmetic composition for improving skin condition containing a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
  • the term “improvement” may mean any action that reduces at least the severity of a parameter, such as a symptom, related to the alleviation or treatment of a condition.
  • skin condition improvement may comprehensively refer to the process or effect of treating, alleviating, or alleviating skin damage caused by intrinsic or extrinsic factors, such as For example, it may be interpreted as showing improvement of wrinkles, improvement of skin elasticity, wound recovery, strengthening of skin barrier, or inhibition of skin aging, but is not limited thereto.
  • wrinkle improvement may refer to all actions that increase the total amount of extracellular matrix factors, including promotion of collagen synthesis.
  • stretchening the skin barrier may mean strengthening the skin's natural function to prevent moisture and nutrients in the skin from leaking out and to prevent harmful substances such as bacteria and viruses from penetrating the skin.
  • inhibiting skin aging may mean suppressing deterioration of skin functions such as wrinkles, sagging skin, and decreased elasticity.
  • the skin aging may be photoaging, for example, skin aging caused by ultraviolet rays.
  • the cosmetic composition according to one embodiment contains a peptide consisting of 10 or less amino acids as an active ingredient, and accordingly, the skin penetration rate of the active ingredient is very excellent, and, for example, it can be applied topically to the skin. In this case, the skin condition can be effectively improved.
  • the peptide can be used as an active ingredient in a cosmetic composition for improving skin condition.
  • the cosmetic composition contains a cosmetically effective amount of the peptide; and/or may include a cosmetically acceptable carrier, but are not limited thereto.
  • cosmetically effective amount refers to an amount sufficient to achieve the skin condition improvement effect of the cosmetic composition.
  • the weight ratio between the peptide and the cosmetically acceptable carrier may be, for example, 500:1 to 1:500, and as examples, the weight ratio is 450:1 to 1:450, 400:1 to 1:400, and 350:1. :1 to 1:350, 300:1 to 1:300, 250:1 to 1:250, 200:1 to 1:200, 150:1 to 1:150, 100:1 to 1:100, 80:1 to 1:80, 60:1 to 1:60, 40:1 to 1:40, 20:1 to 1:20, 10:1 to 1:10, 8:1 to 1:8, 6:1 to 1 :6, 4:1 to 1:4, or 2:1 to 1:2, but is not limited thereto.
  • the cosmetic composition can be prepared in any formulation commonly prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil. , may be formulated as powder foundation, emulsion foundation, wax foundation, spray, etc., but is not limited thereto. For example, it can be manufactured in the form of softening lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, or powder.
  • the formulation of the cosmetic composition is paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier ingredients. It can be.
  • the formulation of the cosmetic composition is a powder or spray
  • lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as the carrier ingredient.
  • chlorofluoro may be additionally used. May contain propellants such as hydrocarbons, propane/butane or dimethyl ether.
  • a solvent, solubilizing agent, or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, It may include 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.
  • the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, and miso.
  • a liquid diluent such as ethanol or propylene glycol
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester
  • miso Crystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.
  • the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid.
  • Amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.
  • the peptide may be contained in nanosomes or nanoparticles to further improve skin penetration or stability problems.
  • the nanosomes can be manufactured with a microfluidizer using lecithin as a raw material and can be contained in lecithin particles. Any method for producing the nanosomes can be used as long as it is known.
  • the size of the nanosome particles is preferably 30 to 200 nm. If the size of the nanosome particles is less than 30 nm, skin penetration progresses very quickly and skin side effects may occur, and if it exceeds 200 nm, skin penetration is not easy, making it difficult to obtain the effect of using the nanosome structure. there is.
  • Ingredients included in the cosmetic composition include, in addition to peptides as active ingredients and carrier components, ingredients commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances. May contain phosphorus supplements.
  • the content of the peptide as an active ingredient contained in the cosmetic composition can be appropriately selected without limitation depending on the form of the product, desired use, etc., for example, it can be added at 0.01 to 15% by weight of the total weight of the cosmetic composition. there is.
  • the cosmetic composition may include 1.0 wt% to 3.0 wt%, preferably 2.0 wt% to 3.0 wt%, of the peptide based on the total weight.
  • Another aspect is a method of improving skin condition, comprising applying a cosmetic composition containing a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient to the skin of an individual; Provided is the use of a peptide consisting of the amino acid sequence of SEQ ID NO: 1 for the production of a composition for improving skin condition.
  • the term “individual” refers to a subject in need of skin condition improvement, and more specifically, human or non-human primates, mice, dogs, cats, horses, and cattle. refers to mammals such as
  • applying As used herein, the terms “applying,” “administering,” and “applying” are used interchangeably and refer to at least partial localization of a composition to a desired area, or route of administration, according to one embodiment. This may mean disposing the composition according to one embodiment into an object.
  • Another aspect provides an antioxidant composition containing a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
  • the antioxidant composition may be in the form of a pharmaceutical composition, a quasi-drug composition, or a cosmetic composition.
  • the composition is a cosmetic composition for improving skin condition, or a drug for improving or treating the condition of a disease related to skin damage. It can be used as an academic composition.
  • the peptide was shown to be able to restore the inhibited activity of fibroblasts and keratinocytes and enhance their antioxidant efficacy. Therefore, the peptide can be used as an active ingredient in an antioxidant composition.
  • the antioxidant composition may be provided in the form of a pharmaceutical composition.
  • the pharmaceutical composition contains a pharmaceutically effective amount of the peptide; and/or may include a pharmaceutically acceptable carrier, but are not limited thereto.
  • the term “pharmaceutically effective amount” may mean an amount sufficient to achieve the efficacy of the pharmaceutical composition in preventing or treating diseases related to skin damage.
  • the pharmaceutically acceptable carriers are commonly used in formulations and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Includes, but is not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
  • the weight ratio between the peptide and the pharmaceutically acceptable carrier may be, for example, 500:1 to 1:500, and as examples, the weight ratio is 450:1 to 1:450, 400:1 to 1:400, 350:1 :1 to 1:350, 300:1 to 1:300, 250:1 to 1:250, 200:1 to 1:200, 150:1 to 1:150, 100:1 to 1:100, 80:1 to 1:80, 60:1 to 1:60, 40:1 to 1:40, 20:1 to 1:20, 10:1 to 1:10, 8:1 to 1:8, 6:1 to 1 :6, 4:1 to 1:4, or 2:1 to 1:2, but is not limited thereto.
  • the pharmaceutical composition may further include, but is not limited to, lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.
  • the pharmaceutical composition can be administered orally or parenterally, preferably parenterally, and in the case of parenteral administration, it can be administered by intramuscular injection, intravenous injection, subcutaneous injection, intraperitoneal injection, topical administration, transdermal administration, etc. , but is not limited to this.
  • the dosage of the pharmaceutical composition may be 0.0001 to 1000 ug (microgram), 0.001 to 1000 ug, 0.01 to 1000 ug, 0.1 to 1000 ug, or 1.0 to 1000 ug per day, but is not limited thereto. It can be prescribed in various ways depending on factors such as method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity.
  • the pharmaceutical composition is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by a person skilled in the art to which the invention pertains. It can be manufactured by placing it in a multi-capacity container.
  • the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally contain a dispersant and/or stabilizer.
  • Another aspect provides a food composition for improving skin condition containing a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
  • the content of the peptide as an active ingredient contained in the food composition can be appropriately selected without limitation depending on the form of the food, desired use, etc., for example, it can be added at 0.01 to 15% by weight of the total weight of the food. . Also, for example, the health drink composition may be added at a rate of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 ml.
  • the peptide according to one aspect can be used as an active ingredient in a composition for improving skin condition.
  • Figure 1 shows the results of adding a peptide consisting of the amino acid sequence of SEQ ID NO: 1 to NIH3T3 cells, and confirming the level of cell proliferation as a change in cell survival rate.
  • Figure 2 shows the results confirming the increase in expression of extracellular matrix components Col1a1, fibronectin, and elastin after adding the peptide consisting of the amino acid sequence of SEQ ID NO: 1 to NIH3T3 cells.
  • Figure 3 is a quantitative evaluation of the expression level of extracellular matrix components after adding a peptide consisting of the amino acid sequence of SEQ ID NO: 1 to NIH3T3 cells.
  • Figure 3A shows the result of confirming the expression level of Col1a1
  • Figure 3 Figure 3B is the result of confirming the expression level of fibronectin
  • Figure 3C is the result of confirming the expression level of elastin.
  • Figure 4 shows the results confirming the increase in expression of skin barrier factors SIRT-1 and AQP3 after adding the peptide consisting of the amino acid sequence of SEQ ID NO: 1 to HaCaT cells.
  • Figure 5 is a quantitative evaluation of the expression level of skin barrier factors after adding a peptide consisting of the amino acid sequence of SEQ ID NO: 1 to HaCaT cells.
  • Figure 5A shows the result of confirming the expression level of SIRT-1
  • Figure 5 shows the quantitative evaluation of the expression level of skin barrier factors.
  • B in 5 is the result of confirming the expression level of AQP3.
  • Figure 6 shows the results of quantitatively confirming the change in the level of reactive oxygen species increased by ultraviolet rays after adding the peptide consisting of the amino acid sequence of SEQ ID NO: 1 to HaCaT cells.
  • NIH3T3 cells were seeded in a 96-well plate at a density of 1x10 4 cells/well, and then cultured for 24 hours. Afterwards, the cells were washed once with serum-free DMEM media, and the peptide consisting of the amino acid sequence of SEQ ID NO. 1 was dispensed at 50 ⁇ M or 100 ⁇ M into 200 ⁇ L of the serum-free medium, and incubated at 37°C. Cultured in a CO 2 incubator for 72 hours. Afterwards, the culture was washed twice with PBS, and then MTT solution was dispensed into each well at 0.5 mg/ml. Afterwards, it was shielded from light and cultured in a CO 2 incubator at 37°C for 4 hours, and the absorbance was measured at 540 nm using a microplate reader (Molecular Devices, USA).
  • NIH3T3 cells were seeded in a 6-well plate at a density of 3 ⁇ 10 5 cells/well and then cultured for 24 hours. Afterwards, the cells were washed once with serum-free DMEM media, and then 10 ⁇ M, 50 ⁇ M, or 100 ⁇ M of the peptide consisting of the amino acid sequence of SEQ ID NO. 1 was dispensed into 1 mL of the medium, and the mixture was incubated at 37°C. Cultured for 24 hours in a CO 2 incubator. Afterwards, the culture was washed twice with PBS, and RNA was isolated from the culture using easy blue (iNtRON, Cat. No.: 17061, Korea).
  • easy blue iNtRON, Cat. No.: 17061, Korea
  • RNA was reverse transcribed to synthesize each cDNA.
  • PCR polymerase chain reaction
  • the synthesized 1 ⁇ g cDNA primers for Col1a1, fibronectin, or elastin, and a PCR kit (enzynomics, Cat. No.: P581T, Korea).
  • the untreated group was used as the control group, and the group to which IGF was added was used as the positive control group.
  • the nucleotide sequences of the primers used in this example are shown in Table 2 below.
  • the effect of the peptide according to one embodiment on strengthening the skin barrier was attempted to be confirmed by evaluating the expression level of sirtuin-1 (SIRT-1) or aquaporin-3 (AQP3).
  • HaCaT cells were seeded in a 6-well plate at a density of 3 ⁇ 10 5 cells/well and then cultured for 24 hours. Afterwards, the cells were washed once with serum-free DMEM media, and then 10 ⁇ M, 50 ⁇ M, or 100 ⁇ M of the peptide consisting of the amino acid sequence of SEQ ID NO. 1 was dispensed into 1 mL of the medium, and the mixture was incubated at 37°C. Cultured for 24 hours in a CO 2 incubator. Afterwards, the culture was washed twice with PBS, and RNA was isolated from the culture using easy blue (iNtRON, Cat. No.: 17061, Korea). Afterwards, using an RT kit (Enzynomics, Cat.
  • RNA was reverse transcribed to synthesize each cDNA.
  • a polymerase chain reaction PCR was performed using 1 ⁇ g of the synthesized cDNA, primers for SIRT-1 or AQP3, and a PCR kit (enzynomics, Cat. No.: P581T, Korea). did.
  • the untreated group was used as the control group, and the group to which EGF was added was used as the positive control group.
  • the nucleotide sequences of the primers used in this example are shown in Table 3 below.
  • HaCaT cells were seeded in a 6-well plate at a density of 5 ⁇ 10 5 cells/well and then cultured for 24 hours. Afterwards, the cells were washed once with serum-free DMEM media, and then 50 ⁇ M or 100 ⁇ M of the peptide consisting of the amino acid sequence of SEQ ID NO. 1 was dispensed into 1 mL of the medium and incubated at 37°C. Cultured for 1 hour in a CO 2 incubator. Afterwards, the culture was transferred to an e-tube, mixed with 1ml of PBS, and dispensed into a well-plate.
  • the cells were washed twice with PBS, treated with 500 ⁇ L of 1 ⁇ trypsin/EDTA to obtain cells, and then centrifuged. After centrifuged cells were washed with PBS, fluorescence values were measured through flow cytometry (FACS, BD, USA).
  • the control group was an untreated group
  • the comparison group (NC) was a group irradiated only with ultraviolet rays
  • the positive control group was a group to which 50 ⁇ M of Trolox was added.
  • Example 1 50 mg of the peptide of Example 1 was dissolved in 500 ml of distilled water by sufficiently stirring. After mixing the mixture solution with 5 g of lecithin, 0.3 ml of sodium oleate, 50 ml of ethanol, and a little oil phase, adjust the amount with distilled water so that the total amount is 1 L, and then use a microfluidizer. Peptide nanosomes with a size of about 100 nm were prepared by emulsifying them using high pressure.
  • a soft water lotion containing a peptide according to an example and having the following composition was prepared using a method known in the art.
  • a nutritional cream containing a peptide according to an example and having the following composition was prepared using a method known in the art.
  • a nutritional lotion containing a peptide according to an example and having the following composition was prepared using a method known in the art.

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Abstract

La présente demande porte sur un peptide ayant une activité d'amélioration de l'état de la peau et son utilisation et concerne un peptide constitué de la séquence d'acides aminés de SEQ ID NO : 1 et une composition cosmétique pour améliorer l'état de la peau comprenant, en tant que principe actif, le peptide constitué par la séquence d'acides aminés de SEQ ID NO : 1.
PCT/KR2022/018719 2022-11-18 2022-11-24 Peptide ayant une activité d'amélioration de l'état de la peau et son utilisation WO2024106588A1 (fr)

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KR1020220155814A KR20240086710A (ko) 2022-11-18 2022-11-18 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도
KR10-2022-0155814 2022-11-18

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110318284A1 (en) * 2010-06-29 2011-12-29 Isp Investments Inc. Novel sirtuin 6 activating peptides and cosmetic or pharmaceutical composition containing them
KR20180019960A (ko) * 2016-08-17 2018-02-27 (주)진셀팜 주름 개선 및 항노화 효과를 가지는 펩타이드, 및 이의 용도
KR101912230B1 (ko) * 2017-09-27 2018-10-26 주식회사 펠리즈코스 피부 상태 개선을 위한 펩타이드 조성물 및 그 용도
KR102265430B1 (ko) * 2019-08-20 2021-06-15 주식회사 케어젠 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110318284A1 (en) * 2010-06-29 2011-12-29 Isp Investments Inc. Novel sirtuin 6 activating peptides and cosmetic or pharmaceutical composition containing them
KR20180019960A (ko) * 2016-08-17 2018-02-27 (주)진셀팜 주름 개선 및 항노화 효과를 가지는 펩타이드, 및 이의 용도
KR101912230B1 (ko) * 2017-09-27 2018-10-26 주식회사 펠리즈코스 피부 상태 개선을 위한 펩타이드 조성물 및 그 용도
KR102265430B1 (ko) * 2019-08-20 2021-06-15 주식회사 케어젠 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE Protein 6 March 2021 (2021-03-06), "hypothetical protein [Streptomyces sp. ICN441]", XP093171663, Database accession no. WP_206307230.1 *

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